Increased monocyte to high-density lipoprotein cholesterol ratio is associated with TIMI risk score in patients with ST-segment elevation myocardial infarction

Introduction and Aim

The monocyte to high-density lipoprotein cholesterol ratio (MHR) has recently been proposed as a new predictor and prognostic indicator in cardiovascular disease. The TIMI risk score predicts short-term mortality in ST-elevation myocardial infarction (STEMI) patients. However, there have been no studies regarding the association between MHR and TIMI score in patients with STEMI.

Triglycerides and high-density lipoprotein cholesterol are associated with insulinemia in adolescents

OBJECTIVE: The aim of this study was to evaluate the association between lipids and insulin concentration in adolescents. MATERIAL AND METHODS: A cross-sectional study of 350 adolescents aged 14-19 years old from a public high school in Guadalajara, in the state of Jalisco, Mexico, was conducted. Fasting insulin concentration was determined using microparticle enzyme immunoassay; total cholesterol and triglycerides were detected by standard enzymatic procedures;and low- and high-density lipoproteins were found using standard precipitation methods. Statistical analysis included linear multivariate regression. RESULTS: Serum triglycerides were associated positively with insulin fasting (beta = 0.003, p = 0.0001) and high-density lipoprotein cholesterol was negatively associated with insulin fasting in male adolescents 18-19 years old (beta = -0.03, p = 0.012). CONCLUSIONS: The relationships between triglycerides and insulin and between high-density lipoprotein cholesterol and insulin are already present in adolescence.     

When high is low: Raising low levels of high-density lipoprotein cholesterol

Low serum levels of high-density lipoprotein cholesterol (HDL-C) are highly prevalent and are recognized as an independent risk factor for cardiovascular morbidity (myocardial infarction, stroke, peripheral arterial disease, and restenosis after coronary stenting) and mortality. HDL plays an important role in modulating atherogenesis, although its functions are varied and complex and the mechanisms for its antiatherogenic effects have not been completely elucidated. The inverse relationship between HDL-C and cardiovascular risk is well established, and epidemiologic studies and clinical trials have provided ample evidence that higher levels of HDL-C are vasculoprotective. Although considerable interest exists in the development of novel approaches to raise serum HDL-C and to augment HDL functionality, this article discusses currently available therapies to raise suboptimal levels of this important lipoprotein.     

Postprandial lipemia in postmenopausal women with high fasting high-density lipoprotein cholesterol

BACKGROUND: Several groups of patients at high risk for cardiovascular disease have been found to show an exaggerated postprandial hypertriglyceridemia. Postprandial lipemia (PPL) therefore has been implicated as a potential additional risk factor that has been evading us. The purpose of this study was to test the effect of high fasting high-density lipoprotein cholesterol (HDL-C) levels on PPL in postmenopausal females. METHODS: Oral fat tolerance test, as quantified by the areas under the curve (AUC) of triglyceride (TG) levels, was given to 3 groups: normal postmenopausal females (control), postmenopausal females with exceptionally high HDL-C and a familial history of longevity (longevity syndrome), and postmenopausal females that were heterozygotes of familial hypercholesterolemia (hFH) with exceptionally high HDL-C. RESULTS: The PPL was not different between the control and longevity syndrome groups but was significantly higher in the hFH group; AUC (SD), in mg/dl/h; 749 (195), 882 (278) and 1244 (497) respectively, p=0.002. In linear regression analysis only fasting TG levels were a significant predictor of the AUC (Coefficient B = 11.779, p < 0.001). CONCLUSIONS: In subjects with longevity syndrome the PPL is similar to controls, which means that high fasting HDL-C has not any beneficial influence on PPL. The fasting TG concentration is the main determinant of PPL. Furthermore, postmenopausal females with hFH have higher TG response postprandially, even in the case of high fasting HDL-C. Whether there is a threshold below or above, where HDL-C becomes a significant independent determinant of PPL is a question to be answered by future research.     

Effect of low-dose niacin on high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein cholesterol ratio

Niacin significantly alters blood lipid concentrations but its use has been limited because of clinically disturbing side effects. In an attempt to circumvent these drawbacks, 55 patients with cardiovascular disease were given low-dose long-acting niacin, 1 g/d. Treatment was continued for a mean of 6.7 months and lipid values were compared with a non-treated group of 17 patients followed for a mean of 6.3 months. Lipid values did not change in the nontreated group. In the niacin-treated group total cholesterol and triglyceride levels also did not significantly change. High-density lipoprotein (HDL) cholesterol level rose 31% from 1.01 +/- 0.31 mmol/L to 1.32 +/- 0.31 mmol/L and total cholesterol/HDL cholesterol ratio was reduced 27% from 6.4 +/- 1.9 to 4.7 +/- 1.3. Despite these results, 40% of the patients left the study mainly because of side effects. Apart from one patient who developed overt diabetes, of questionable relationship to niacin, no patient developed serious side effects such as jaundice or peptic ulcer as seen with much higher doses of the drug. Although often difficult to administer to patients, niacin, particularly in low dose, deserves consideration as an inexpensive agent especially useful for elevating HDL cholesterol level and altering the total cholesterol/HDL cholesterol ratio.     

Serum adiponectin is associated with high-density lipoprotein cholesterol, triglycerides, and low-density lipoprotein particle size in young healthy men

The chromosomal localization of adiponectin has been found to be mapped to human chromosome 1q21.4-1q23, a region that was identified as a susceptibility locus for familial combined hyperlipidemia and polygenic type 2 diabetes. As these 2 disorders are associated with low high-density lipoprotein (HDL)-cholesterol, high triglycerides, and insulin resistance (IR), we examined the relation of serum adiponectin concentrations to serum lipid and lipoprotein profiles as well as IR in young healthy men. Serum adiponectin levels were positively associated with HDL-cholesterol, apolipoprotein (apo) A1, and low-density lipoprotein (LDL) particle size, and negatively associated with triglycerides and apo B. Negative associations were also found between adiponectin and body mass index (BMI), percent body fat, and IR,as determined by homeostasis model assessment (HOMA). However, after adjustment for BMI, no significant associations were found between adiponectin and LDL particle size and apo B. In a multiple regression analysis including all variables that showed significant univariate associations with adiponectin, associations of adiponectin with HDL-cholesterol (beta = 0.079, P =.0009), percent body fat (beta = -0.165, P =.002), and serum leptin (beta = -0.291, P =.01) were statistically significant. HDL-cholesterol (beta = 0.077, P =.001), percent body fat (beta = -0.078, P =.03), and LDL size (beta = 0.092, P =.03) emerged as significant and independent determinants of adiponectin after HOMA IR, fasting glucose, triglycerides, and systolic blood pressure (BP) were taken into account. Together, these variables explained 19% of adiponectin variability in the 2 models. HOMA IR did not emerge as a determinant of adiponectin in both models. These findings suggest that in young healthy men hypoadiponectinemia is more closely related to adiposity and dyslipidemia than IR.     

Increased apolipoprotein E level and reduced high-density lipoprotein mean particle size associate with low high-density lipoprotein cholesterol and features of metabolic syndrome

The metabolic syndrome (MetS) pandemic predisposes patients to low high-density lipoprotein cholesterol (HDL-C). To successfully treat low HDL-C, there is an urgent need for a better understanding of the changes in HDL particles in the low-HDL-C state. Especially, apolipoprotein (apo) E metabolism in HDL particles is an emerging and important issue. Therefore, we determined HDL subspecies, apo E distribution, and the impact of the MetS in subjects with low and high HDL-C. We studied 246 subjects derived from the Finnish Health 2000 Health Examination Survey. The 2 groups included 113 low-HDL-C (≤10th percentile) and 133 high-HDL-C (≥90th percentile) subjects. The low-HDL-C subjects had higher apo E concentration (39.4 ± 19.4 vs 25.6 ± 8.0 μg/mL, P < .001) and smaller HDL mean particle size (9.0 ± 0.2 vs 9.8 ± 0.3 nm, P < .001). The distribution of apo E genetic isoforms could not explain the difference. Apolipoprotein E content of very low-density lipoprotein particles was comparable between the study groups. In the low-HDL-C subjects, apo E level in large HDL particles was lower (P < .001) compared with that in the high-HDL-C subjects. The subjects with MetS had smaller HDL mean particle size and higher serum apo E concentration. Serum apo E concentration associated positively with different MetS markers (waist circumference, triglycerides, and glucose), whereas HDL mean particle size associated with those negatively. Our results highlight that, in the low-HDL-C state, there are changes in the size and composition of HDL particles associating with MetS. Apolipoprotein E, although generally considered antiatherogenic, associates with MetS and low HDL-C. Our results emphasize the need for a better understanding of apo E metabolism in HDL particles.     

Biliary cholesterol hypersecretion in gallstone-susceptible mice is associated with hepatic up-regulation of the high-density lipoprotein receptor SRBI

Enhanced hepatocellular trafficking of cholesterol to the bile canaliculus and cholesterol hypersecretion appears critical for gallstone formation. Therefore, we studied in more detail the hepatic cholesterol transport pathways in a mouse model of cholesterol gallstone disease. Biliary lipid secretion rates, plasma lipoprotein levels, hepatic expression of lipoprotein receptors, lipid regulatory enzymes, and putative cholesterol transporting proteins were analyzed in gallstone-susceptible C57L/J and gallstone-resistant AKR/J mice, which were fed a lithogenic diet. Biliary cholesterol hypersecretion in C57L mice was associated with decreased plasma high-density lipoprotein (HDL) cholesterol levels and significant hepatic induction of the HDL receptor (SRBI) and cholesteryl ester hydrolase. In response to the lithogenic diet, fatty-acid binding protein of liver (FABPL) was markedly induced in both mouse strains. Caveolin 1 was elevated only in plasma membranes of gallstone-susceptible C57L mice, which also failed to down-regulate cholesterol synthesis. These data suggest a role of the reverse cholesterol transport pathway for genetically determined gallstone susceptibility in the mouse.     

Alcohol consumption is associated with enrichment of high-density lipoprotein particles in polyunsaturated lipids and increased cholesterol esterification rate

BACKGROUND: Alcohol consumption is associated with high levels of high-density lipoproteins (HDLs). Moreover, changes in the fatty acid patterns of red blood cell phospholipids and plasma lipids have been observed in drinkers. The objectives of this study were to characterize the composition of HDL particles with respect to lipid molecular species in regular wine drinkers and to assess the functional properties of those HDLs as regards key steps of reverse cholesterol transport. METHODS: Forty-six subjects were recruited in the frame of a population study performed in Toulouse, southern France, and a nutritional investigation, including daily alcohol consumption, was performed. Subjects were sorted according to their daily alcohol intake (0, < or =35, and >35 g/day), mostly as red wine. The plasma HDL fraction was isolated, and neutral lipid molecular lipids and phospholipid fatty acids were analyzed by gas liquid chromatography. Efflux of cellular cholesterol and rates of cholesterol esterification and cholesteryl ester transfers between lipoproteins were assayed in a cell-plasma incubation system. RESULTS: Wine drinking, at 47 g/day, was associated with an increase in HDL cholesterol and apolipoprotein A-I, but not with triglycerides. Isolated HDL displayed a 27% increase in all cholesteryl ester molecular species. The particles were also enriched in unsaturated phospholipids and, particularly, in those containing arachidonic (+30%) and eicosapentaenoic (+90%) acids. The plasma cholesterol esterification rate, reflecting lecithin cholesterol acyl transferase activity on HDL, was found to be higher (+27%) in drinkers than in nondrinkers, whereas the rate of cellular cholesterol efflux to plasma was identical. CONCLUSIONS: Regular wine consumption is associated with high levels of polyunsaturated lipids in HDL and with increases in the cholesterol esterification rate.     

Increased serum high-density lipoprotein cholesterol in hypertensive men treated with the potent vasodilator carprazidil

The effects of the potent arteriolar vasodilator carprazidil on serum lipoproteins and various clinical, biochemical and endocrine parameters were assessed in 15 men with mild to moderate essential hypertension. Following a carprazidil monotherapy (average dose 50 to 60 mg/d) of 8 weeks (N = 15) or 16 weeks (N = 12) duration, blood pressure was decreased significantly (P less than 0.01), while serum high-density lipoprotein cholesterol (+ 26% and + 24%, respectively; P less than 0.01) and the alpha-lipoprotein fraction (+ 26% and + 41%) were increased. Low- and very low-density lipoprotein cholesterol, triglycerides, as well as mean body weight, blood and plasma volume, heart rate, and plasma renin, aldosterone, norepinephrine, and epinephrine were not consistently altered. These results indicate that treatment of hypertensive men with carprazidil in modest dosage may have a favorable influence both on blood pressure and serum lipoproteins.     

The value of serum albumin and high-density lipoprotein cholesterol in defining mortality risk in older persons with low serum cholesterol

OBJECTIVES: To investigate the relationship between low cholesterol and mortality in older persons to identify, using information collected at a single point in time, subgroups of persons with low and high mortality risk. DESIGN: Prospective cohort study with a median follow-up period of 4.9 years. SETTINGS: East Boston, Massachusetts; New Haven, Connecticut; and Iowa and Washington counties, Iowa. PARTICIPANTS: Four thousand one hundred twenty-eight participants (64% women) age 70 and older at baseline (mean 78.7 years, range 70-103); 393 (9.5%) had low cholesterol, defined as < or =160 mg/dl. MEASUREMENTS: All-cause mortality and mortality not related to coronary heart disease and ischemic stroke. RESULTS: During the follow-up period there were 1,117 deaths. After adjustment for age and gender, persons with low cholesterol had significantly higher mortality than those with normal and high cholesterol. Among subjects with low cholesterol, those with albumin> 38 g/L had a significant risk reduction compared with those with albumin < or =38 g/L (relative risk (RR) = 0.57; 95% confidence interval (CI) = 0.41-0.79). Within the higher albumin group, high-density lipoprotein cholesterol (HDL-C) level further identified two subgroups of subjects with different risks; participants with HDL-C <47 mg/dl had a 32% risk reduction (RR = 0.68; 95% CI = 0.47-0.99) and those with HDL-C > or =47 mg/dl had a 62% risk reduction (RR = 0.38; 95% CI = 0.20-0.68), compared with the reference category; those with albumin < or =38 g/L and HDL-C <47 mg/dl. CONCLUSIONS: Older persons with low cholesterol constitute a heterogeneous group with regard to health characteristics and mortality risk. Serum albumin and HDL-C can be routinely used in older patients with low cholesterol to distinguish three subgroups with different prognoses: (1) high risk (low albumin), (2) intermediate risk (high albumin and low HDL-C), and (3) low risk (high albumin and high HDL-C).     

Obesity is associated with functional decline in community-dwelling rural older persons

OBJECTIVES: This investigation sought to examine potential gender differences in the relationship between body mass index (BMI) and functional decline. DESIGN: Cohort study. SETTING: Rural Pennsylvania. PARTICIPANTS: Medicare managed-risk program participants (aged > or =65) in the Geisinger Health Plan. Mean age at study baseline was 71. Final analyzable sample was 2,634 participants. MEASUREMENTS: Self-reported weight, weight change, living and eating habits, alcohol and medication use, depression, dentition, and functional status were obtained upon enrollment and again between 3 and 4 years later. Measured height and weight were also recorded at enrollment. Functional decline was defined as any increase in reported limitations in activities of daily living or instrumental activities of daily living over the study period. Logistic regression was used to evaluate the relationship between BMI, as defined by current National Institutes of Health categories, and risk of functional decline while controlling for age, depression, and polypharmacy. The referent category was BMI 18.5 to 24.9. RESULTS: Women had a higher prevalence of reported functional decline than men at the upper range of BMI categories (31.4% vs 14.3% for BMI > or =40). Women (odds ratio (OR) = 2.61, 95% confidence interval (CI) = 1.39-4.95) and men (OR = 3.32, 95% CI = 1.29-8.46) exhibited increased risk for any functional decline at BMI of 35 or greater. Weight loss of 10 pounds and weight gain of 20 pounds were also risk factors for any functional decline. CONCLUSIONS: Obesity was a risk factor for functional decline in older persons of either gender. Change in body weight did not benefit function for many older persons.     

Serum high-density lipoprotein cholesterol levels as a prognostic indicator in patients with idiopathic pulmonary arterial hypertension

High-density lipoprotein (HDL) cholesterol levels are a strong, independent inverse predictor of cardiovascular disease. The present study aimed to determine whether serum HDL cholesterol levels correlated with disease severity and clinical outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH). The serum HDL cholesterol levels were measured in 76 Chinese patients with IPAH and 45 healthy controls, together with other clinical variables. Univariate and multivariate Cox proportional hazards analysis was performed to assess the prognostic value of HDL cholesterol and event-free survival. Event-free survival was estimated using the Kaplan-Meier method. Serum HDL cholesterol levels were significantly decreased in patients with IPAH compared with controls (1.0 ± 0.3 vs 1.5 ± 0.3 mmol/L; p <0.001). The serum HDL cholesterol levels decreased in proportion to the severity of World Health Organization functional class. Compared to the high HDL cholesterol group, the low HDL cholesterol group demonstrated a significantly lower 6-minute walking distance, cardiac index, mixed venous saturation, and arterial carbon dioxide pressure but significantly greater pulmonary vascular resistance and serum uric acid levels. The serum HDL cholesterol levels correlated positively with the cardiac index (r = 0.42; p = 0.002) and negatively with the pulmonary vascular resistance (r = -0.25; p = 0.04). Serum HDL cholesterol was independently related to event-free survival on multivariate Cox proportional hazards analysis. Kaplan-Meier survival curves according to the median HDL cholesterol value showed that lower HDL cholesterol levels were associated with lower event-free survival. In conclusion, serum HDL cholesterol levels might serve as an indicator of disease severity and prognosis in patients with IPAH.